Analgesic efficacy of low-dose ketamine: Somatosensory-evoked responses in relation to subjective pain ratings

Background: Low-dose ketamine has been shown to exert analgesic effects. Whether ketamine-induced pain relief may be quantitated by somatosensory evoked cerebral potentials has not been established. Methods: Thirty healthy volunteers were assigned randomly to one of three groups. Subjects of group 1(n = 10, control) were given saline as placebo. In groups 2(n = 10) and 3 (n = 10), intravenous ketamine (0.25 mg · kg^-1 and 0.50 mg · kg^-1, respectively) was administered. The following variables were recorded at baseline and for 50 min after drug administration: electroencephalographic (EEG) data, somatosensory-evoked late cortical responses (SEP) elicited by intracutaneous stimulation of the fingertip (2- 3 fold pain threshold), heart rate, mean arterial blood pressure, and end- tidal PET(CO₂) via a tight-fitting task. Electroencephalographic spectral power in selected frequency bands and frequency percentiles were calculated from the spontaneous EEG segment preceding each somatosensory stimulus. Somatosensory-evoked late cortical response parameters were calculated from the respective poststimulus EEG segments. After recording of each EEG response, subjects were asked to rate the individual pain sensation. Results: In group 1, all variables did not change over time. Ketamine administration resulted in dose-dependent decreases in alpha-activity and increases in theta power (group 2: 190%, group 3: 440%). Electroencephalographic changes were not related to changes in pain perception. For the first 30 min after ketamine injection, a dose-dependent decrease of the long-latency N₁₅₀-P₂₅₀ somatosensory-evoked late cortical response component was observed (group 2: 15-20%; group 3: 25- 30%). Subjective pain ratings were also different between groups, with a higher degree of pain relief in group 3 for the first 30 min. At the end of the observation period, pain relief and the N₁₅₀-P₂₅₀ amplitude were comparable in both ketamine groups. Conclusions: These data indicate that pain relief induced by low-dose ketamine is dose-dependent for the first 30 min after bolus injection. Changes in pain perception may be quantitated by somatosensory-evoked cortical responses. Also. EEG changes are not specific for changes in nociception, but the increase in theta power may reflect the hypnotic effect of low-dose ketamine.